Duke University proposes to replace, update, and enhance failing components of its 600 MHz NMR spectroscopy system with a new console, cryo-system, and 1H{13C/15N} 5mm 13C-enhanced cold probe. The 600 MHz spectrometer is housed in and is managed by the Duke NMR Spectroscopy Center that serves as an NMR resource for all University research projects and for scientists at universities and government laboratories in the Research Triangle and the Southeastern region. It supports, facilitates and trains scientists in the use of NMR for frontier research in basic biochemical and biomedical sciences. The requested new equipment components are needed to replace a 12-year-old console and 8-year-old cryo- system and probe that are now failing at an unacceptable rate. These component failures have significantly impacted research activities of numerous investigators who depend on the Duke 600 MHz instrument to pursue their funded projects. The instrument is fully subscribed with requests that exceed a 24/7 schedule. Recently, however, the available time has been limited due to unanticipated maintenance and repairs associated with failure of critical components in the console and our first generation cryo-system and cold probe as they have aged. This limitation in the instrument time available for research is compounded by the fact that the Varian Inova console is no longer manufactured, is two generations out of date, and has been replaced by a new generation Agilent DirectDrive2 spectrometer. New parts for our system are no longer manufactured and refurbished, used parts, are often not immediately available either. The new equipment components requested for our 600 MHz NMR system provides a cost effective strategy to restore and enhance this workhorse spectrometer at a cost of approximately half that of a new system since our 14.09T Oxford magnet is in excellent condition and performs with superior homogeneity and negligible drift. Current research activities in the following areas will be enhanced by this upgrade to the Duke 600 MHz NMR spectrometer: studies of protein assemblies; protein conformational dynamics and folding; membrane associated lipids and enzymes involved in their synthesis; enzyme structural characterization and redesign; in-cell NMR spectroscopy of proteins; antibody recognition of immunogenic peptides and phospholipids associated with HIV vaccine design; cellular signaling; and methods development for rapid acquisition of multidimensional NMR data.